ALTERATION OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR AFTER 6-HOUR HEMISPHERIC ISCHEMIA IN THE GERBIL BRAIN

In order to evaluate the influence of cerebral ischemia on the inosito l 1,4,5-trisphosphate receptor, the alterations of inositol I,4,5-tris phosphate receptor binding sites and local cerebral blood flow were ex amined 6 h after occlusion of the right common carotid artery in the g erbil brain. The autoradiographic method developed in our laboratory e nabled us to measure both parameters within the same brain. Animals at taining ischemic scores of more than 5, as assessed 1 h after occlusio n, were utilized. The local cerebral blood flow was measured 6 h after occlusion by the C-14]iodoantipyrine method. The inositol 1,4,5-trisp hosphate binding sites were evaluated in vitro using [H-3]inositol 1,4 ,5-trisphosphate as a specific ligand. The local cerebral blood flow f ell below 15 ml/100 g per min in most of the cerebral regions on the o ccluded side. In contrast, a significant reduction in inositol l,4,5-t risphosphate binding sites was noted only in the hippocampus CA 1 on t he occluded side. Inositol 1,4,5-trisphosphate binding tended to decre ase when the values of local cerebral blood flow were below 20 ml/100 g per min in this region. On the other hand, the inositol 1,4,5-trisph osphate receptor immunoreactivity in the brain examined with a monoclo nal antibody against inositol 1,4,5-trisphosphate receptor protein did not reveal any differences between the ischemia and sham groups on bo th sides, suggesting that the inositol 1,4,5-trisphosphate receptors m ay not undergo significant morphological degradation. These findings i ndicate that the suppression of inositol 1,4,5-trisphosphate binding i n the hippocampus CA 1 may be attributable to a regionally specific pe rturbation of the inositol 1,4,5-trisphosphate metabolism in this regi on. Such perturbation may be closely associated with the pathophysiolo gical mechanism of selective ischemic vulnerability of this region.